Clinical Trials /

Stem Cell Transplant From Donors After Alpha Beta Cell Depletion in Children and Adults With T-allo10 Cells Addback

NCT04640987

Description:

The purpose of this study is to determine the safety of a cell therapy, T-allo10, after αβdepleted-HSCT in the hopes that it will boost the adaptive immune reconstitution of the patient while sparing the risk of developing severe Graft-versus-Host Disease (GvHD). The primary objective of Phase 1 is to determine the recommended Phase 2 dose (RP2D) administered after infusion of αβdepleted-HSCT in children and young adults with hematologic malignancies. A Phase 1b extension will occur after dose escalation, enrolling at the RP2D for the T-allo10 cells determined in the Phase 1 portion to evaluate the safety and efficacy of infusion of T-allo10 after receipt of αβdepleted-HSCT. Additionally, Phase 1b aims to explore improvements in immune reconstitution. All participants on this study must be enrolled on another study: NCT04249830

Related Conditions:
  • Hematopoietic and Lymphoid Malignancy
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Stem Cell Transplant From Donors After Alpha Beta Cell Depletion in Children and Adults With T-allo10 Cells Addback
  • Official Title: Phase 1/1b Study of T-allo10 Infusion After HLA-Partially Matched Related or Unrelated TCR αβ+ T-cell/ CD19+ B-cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation (αβ Depleted-HSCT) in Children and Young Adults Affected by Hematologic Malignancies

Clinical Trial IDs

  • ORG STUDY ID: IRB-58549
  • SECONDARY ID: BMT 367 - T-allo10 Alpha Beta
  • NCT ID: NCT04640987

Conditions

  • Hematologic Diseases

Interventions

DrugSynonymsArms
Allogeneic Stem Cell TransplantExperimental: Stem Cell Transplant
T-allo10 cells addbackExperimental: Stem Cell Transplant

Purpose

The purpose of this study is to determine the safety of a cell therapy, T-allo10, after αβdepleted-HSCT in the hopes that it will boost the adaptive immune reconstitution of the patient while sparing the risk of developing severe Graft-versus-Host Disease (GvHD). The primary objective of Phase 1 is to determine the recommended Phase 2 dose (RP2D) administered after infusion of αβdepleted-HSCT in children and young adults with hematologic malignancies. A Phase 1b extension will occur after dose escalation, enrolling at the RP2D for the T-allo10 cells determined in the Phase 1 portion to evaluate the safety and efficacy of infusion of T-allo10 after receipt of αβdepleted-HSCT. Additionally, Phase 1b aims to explore improvements in immune reconstitution. All participants on this study must be enrolled on another study: NCT04249830

Trial Arms

NameTypeDescriptionInterventions
Experimental: Stem Cell TransplantExperimentalThe participant will undergo a stem cell transplant using donor cells that have been manipulated through an investigational device. The participant's cells will then be manipulated via a T-allo10 cell addback. Participants will be followed for outcomes for two years.
  • Allogeneic Stem Cell Transplant
  • T-allo10 cells addback

Eligibility Criteria

        Inclusion Criteria prior to enrollment:

          -  1. Age > 1 months (with minimum weight of 10 Kg) and < 45 years.

          -  2. Patients deemed eligible for allogeneic HSCT under the originating study, NCT
             04249830

          -  3. Patients with life-threatening hematological malignancies for which HSCT has been
             recommended:

               1. High-risk ALL in 1st CR, ALL in 2nd or subsequent CR;

               2. High-risk AML in 1st CR, AML in 2nd or subsequent CR;

               3. Myelodysplastic syndrome;

               4. JMML (Juvenile myelomonocytic leukemia);

               5. Non-Hodgkin lymphomas in 2nd or subsequent CR;

               6. Other hematologic malignancies eligible for stem cell transplantation per
                  institutional standard.

          -  4. All subjects ≥ 18 years of age must be able to give informed consent, or adults
             lacking capacity to consent must have a LAR available to provide consent. For subjects
             <18 years old their LAR (i.e. parent or guardian) must give informed consent.
             Pediatric subjects will be included in age appropriate discussion and verbal assent
             will be obtained for those > 7 years of age, when appropriate.

        Inclusion criteria prior to T-allo10 infusion:

          1. Patient already received αβdepleted-HSCT and has myeloid engraftment.

          2. Absence of active grade II aGvHD requiring >0.5 mg/Kg of steroids or any diagnosis of
             grade III/IVaGvHD.

        Exclusion Criteria prior to MNC collection for Tallo-10 manufacturing.:

          1. Not eligible to receive HSCT on NCT04249830

          2. Received another investigational agent within 30 days of enrollment.

          3. Pregnancy (positive serum or urine beta-HCG) within 7 days of MNC donation.

          4. Patient or donor is not willing or able to undergo an additional non-mobilized
             apheresis for collection of MNC prior to donation of cells for participation in
             NCT04249830.
      
Maximum Eligible Age:45 Years
Minimum Eligible Age:1 Month
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with myeloid engraftment after T-allo10
Time Frame:Through day 35 (+/- 7 days) after αβdepleted-HSCT
Safety Issue:
Description:IR (a surrogate of reduced risk of leukemia recurrence) is defined reaching the threshold of 50CD3+CD4+T-cells/µl by Day+60(+/-10days).

Secondary Outcome Measures

Measure:Number of participants with ≥grade 3 adverse event related to T-allo10 infusion
Time Frame:Through 1 year after αβdepleted-HSCT
Safety Issue:
Description:
Measure:Number of participants with grade II-IV aGvHD
Time Frame:Assessed at day 90 after αβdepleted-HSCT
Safety Issue:
Description:
Measure:Number of participants with grade III-IV aGvHD
Time Frame:Assessed at day 180 after αβdepleted-HSCT
Safety Issue:
Description:
Measure:Number of participants with cGvHD
Time Frame:Assessed at 1 year after αβdepleted-HSCT
Safety Issue:
Description:
Measure:Leukemia-free survival
Time Frame:Assessed at 1 year after αβdepleted-HSCT
Safety Issue:
Description:Leukemia-free survival defined as at the time of enrollment to disease relapse or death from any cause.
Measure:Number of participants with disease relapse
Time Frame:Assessed at 1 year after αβdepleted-HSCT
Safety Issue:
Description:Disease relapse is defined as the return of signs and symptoms of a disease after a remission.
Measure:Non-relapse mortality
Time Frame:Assessed at Day 90 after αβdepleted-HSCT
Safety Issue:
Description:
Measure:Non-relapse mortality
Time Frame:Assessed at 1 year after αβdepleted-HSCT
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Stanford University

Last Updated

November 23, 2020